A large number of polypeptides have been approved for use in medical practice. These polypeptides may be produced in suitable host cells by recombinant DNA technology or they may be produced synthetically by well established peptide synthesis technology. However, native polypeptides as well as analogues and derivatives thereof tend to exhibit high clearance rates which are unacceptable for many clinical indications where a high plasma concentration of the peptide is required over a prolonged period of time. Examples of peptides that in their native form having a high clearance rate are: ACTH, corticotropin-releasing factor, angiotensin, calcitonin, exendin, exendin-3, exendin-4, insulin, glucagon, glucagon-like peptide-1, glucagon-like peptide-2, insulin-like growth factor-1, insulin-like growth factor-2, gastric inhibitory peptide, growth hormone-releasing factor, pituitary adenylate cyclase activating peptide, secretin, enterogastrin, somatostatin, somatotropin, somatomedin, parathyroid hormone, thrombopoietin, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, oxytocin, opioids and analogues thereof, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminase, adenosine deaminase and ribonuclease.
While a number of aqueous formulations which stabilize peptide, polypeptide and protein compositions have been identified in the art, the destabilization of peptides, polypeptides and proteins in both formulation solutions and in solution during processing continues to create difficulty, especially in the up- and down-stream processing of these peptides. Consequently, there is a need for new methods which overcome the insufficiencies of the prior art. (Senderhoff et al., J. Pharm. Sc. Vol. 87, No. 2, pp. 183-189, February 1998).
EP 1 396 499 describes a process for stabilizing glucagon-like peptide (GLP-1) compounds.
EP 0 747 390 describes methods of reducing gelation of a fatty acid acylated protein using a citrate buffer.
S. E. Bondos and A. Bicknell Analytical Biochemistry 316 (2003)223-231. Tris(hydroxymethyl)aminomethane is not mentioned as an agent that may promote protein solubility in this article.